Microbiome Alterations in Alcohol Use Disorder and Alcoholic Liver Disease.

Microbiome alterations are emerging as one of the most important factors that influence the course of alcohol use disorder (AUD). Recent advances in bioinformatics enable more robust and accurate characterization of changes in the composition of the microbiome. In this study, our objective was to provide the most comprehensive and up-to-date evaluation of microbiome alterations associated with AUD and alcoholic liver disease (ALD). To achieve it, we have applied consistent, state of art bioinformatic workflow to raw reads from multiple 16S rRNA sequencing datasets. The study population consisted of 122 patients with AUD, 75 with ALD, 54 with non-alcoholic liver diseases, and 260 healthy controls. We have found several microbiome alterations that were consistent across multiple datasets. The most consistent changes included a significantly lower abundance of multiple butyrate-producing families, including Ruminococcaceae, Lachnospiraceae, and Oscillospiraceae in AUD compared to HC and further reduction of these families in ALD compared with AUD. Other important results include an increase in endotoxin-producing Proteobacteria in AUD, with the ALD group having the largest increase. All of these alterations can potentially contribute to increased intestinal permeability and inflammation associated with AUD and ALD.

Alcoholic Liver Disease Is Associated with Elevated Plasma Levels of Novel Advanced Glycation End-Products: A Preliminary Study.

Elucidating the biochemical mechanisms associated with the progression of alcoholic liver disease (ALD) to more advanced stages such as alcoholic hepatitis (AH) remains an important clinical and scientific challenge. Several hypotheses point to the involvement of advanced glycation end-products (AGEs) in alcohol-associated liver injuries. Recently, we determined the structure of a synthetic, melibiose-derived AGE (MAGE), which was an analog of the novel AGE subgroup AGE10. The primary objective of our study was to determine whether AGE10 was associated with alcoholic hepatitis. The secondary objective was to provide a diagnostic accuracy of AGE10 in AH. To achieve this objective, we examined the plasma levels of AGE10 in 65 healthy individuals and 65 patients with AH. The AGE10 level was measured using a competitive ELISA. Our study confirmed that patients with AH had significantly higher plasma concentrations of AGE10 compared with healthy controls (184.5 ± 71.1 µg/mL and 123.5 ± 44.9 µg/mL, respectively; p < 0.001). In addition, AGE10 showed an acceptable performance as a diagnostic marker of AH, with an AUC of 0.78. In conclusion, AH was associated with elevated levels of novel advanced glycation end-product AGE10.

Human Gut Microbiota in Coronary Artery Disease: A Systematic Review and Meta-Analysis.

In recent years, the importance of the gut microbiome in human health and disease has increased. Growing evidence suggests that gut dysbiosis might be a crucial risk factor for coronary artery disease (CAD). Therefore, we conducted a systematic review and meta-analysis to determine whether or not CAD is associated with specific changes in the gut microbiome. The V3-V4 regions of the 16S rDNA from fecal samples were analyzed to compare the gut microbiome composition between CAD patients and controls. Our search yielded 1181 articles, of which 21 met inclusion criteria for systematic review and 7 for meta-analysis. The alpha-diversity, including observed OTUs, Shannon and Simpson indices, was significantly decreased in CAD, indicating the reduced richness of the gut microbiome. The most consistent results in a systematic review and meta-analysis pointed out the reduced abundance of Bacteroidetes and Lachnospiraceae in CAD patients. Moreover, Enterobacteriaceae, Lactobacillus, and Streptococcus taxa demonstrated an increased trend in CAD patients. The alterations in the gut microbiota composition are associated with qualitative and quantitative changes in bacterial metabolites, many of which have pro-atherogenic effects on endothelial cells, increasing the risk of developing and progressing CAD.

Bayesian network meta-analysis of face masks' impact on human physiology.

Several concerns regarding the safety of face masks use have been propounded in public opinion. The objective of this review is to examine if these concerns find support in the literature by providing a comprehensive overview of physiological responses to the use of face masks. We have performed a systematic review, pairwise and network meta-analyses to investigate physiological responses to the use of face masks. The study has been registered with PROSPERO (C RD42020224791). Obtained results were screened using our exclusion and inclusion criteria. Meta-analyses were performed using the GeMTC and meta R packages. We have identified 26 studies meeting our inclusion and exclusion criteria, encompassing 751 participants. The use of face masks was not associated with significant changes in pulsoxymetrically measured oxygen saturation, even during maximal-effort exercises. The only significant physiological responses to the use of face masks during low-intensity activities were a slight increase in heart rate, mildly elevated partial pressure of carbon dioxide (not meeting criteria for hypercarbia), increased temperature of facial skin covered by the mask, and subsequent increase of the score in the rating of heat perception, with N95 filtering facepiece respirators having a greater effect than surgical masks. In high-intensity conditions, the use of face masks was associated with decreased oxygen uptake, ventilation, and RR. Face masks are safe to use and do not cause significant alterations in human physiology. The increase in heart rate stems most likely from increased respiratory work required to overcome breathing resistance. The increase in carbon dioxide is too small to be clinically relevant. An increased rating of heat perception when using face masks results from higher temperature of facial skin covered by the mask.

Co-toxicity of Endotoxin and Indoxyl Sulfate, Gut-Derived Bacterial Metabolites, to Vascular Endothelial Cells in Coronary Arterial Disease Accompanied by Gut Dysbiosis.

Gut dysbiosis, alongside a high-fat diet and cigarette smoking, is considered one of the factors promoting coronary arterial disease (CAD) development. The present study aimed to research whether gut dysbiosis can increase bacterial metabolites concentration in the blood of CAD patients and what impact these metabolites can exert on endothelial cells. The gut microbiomes of 15 age-matched CAD patients and healthy controls were analyzed by 16S rRNA sequencing analysis. The in vitro impact of LPS and indoxyl sulfate at concentrations present in patients' sera on endothelial cells was investigated. 16S rRNA sequencing analysis revealed gut dysbiosis in CAD patients, further confirmed by elevated LPS and indoxyl sulfate levels in patients' sera. CAD was associated with depletion of Bacteroidetes and Alistipes. LPS and indoxyl sulfate demonstrated co-toxicity to endothelial cells inducing reactive oxygen species, E-selectin, and monocyte chemoattractant protein-1 (MCP-1) production. Moreover, both of these metabolites promoted thrombogenicity of endothelial cells confirmed by monocyte adherence. The co-toxicity of LPS and indoxyl sulfate was associated with harmful effects on endothelial cells, strongly suggesting that gut dysbiosis-associated increased intestinal permeability can initiate or promote endothelial inflammation and atherosclerosis progression.

Advanced Glycation End-Products in Common Non-Infectious Liver Diseases: Systematic Review and Meta-Analysis.

BACKGROUND: Excessive intake of fructose, glucose and alcohol is associated with the development of non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD). At the same time, these dietetic factors create an environment favorable for the generation of advanced glycation end-products. For this reason, advanced glycation end-products (AGEs) are hypothesized to play role in the development of NAFLD and ALD. In this systematic review and meta-analysis, we explore the relationship between NAFLD and ALD with AGE levels, including their diagnostic accuracy. METHODS: The systematic review and meta-analysis has been pre-registered with PROSPERO (CRD42021240954) and was performed in accordance with the PRISMA guidelines. Meta-analyses were performed using the meta R package. RESULTS: We have obtained 11 studies meeting our inclusion criteria, reporting data on 1844 participants (909 with NAFLD, 169 with ALD and 766 healthy controls). NAFLD was associated with significantly higher AGE fluorescence and serum N-(carboxyethyl)lysine (CEL) levels. Patients with alcoholic cirrhosis had significantly higher levels of N-(carboxymethyl)lysine (CML). Only individual studies examined AGEs in the context of their diagnostic accuracy. AGE fluorescence distinguished low and moderate steatosis with an AUC of 0.76. The ratio of CML, CEL and pentosidine to a soluble variant of the AGE receptor differentiated patients with NAFLD from healthy controls with high AUC (0.83-0.85). Glyceraldehyde-derived AGE separated non-alcoholic fatty liver (NAFL) from non-alcoholic steatohepatitis (NASH) with acceptable performance (AUC 0.78). CONCLUSIONS: In conclusion, NAFLD and ALD are associated with significantly higher levels of several AGEs. More research is needed to examine the diagnostic accuracy of AGEs, however individual studies show that AGEs perform well in distinguishing NAFL from NASH.

Strategies for Reducing the Impact of Cycling on the Perineum in Healthy Males: Systematic Review and Meta-analysis.

INTRODUCTION: Perineal pressure associated with bicycle riding is the cause of several genitourinary pathologies, most notably Alcock's syndrome and subsequent perineal numbness. The possible link between cycling-induced perineal numbness and erectile dysfunction makes the development of strategies for perineal protection in bicycle users critical. OBJECTIVE: To assess the effectiveness of strategies for reducing the impact of cycling on the perineum in healthy males. METHODS: We have conducted a systematic review and a meta-analysis of studies examining various means of reducing the impact of cycling on the perineum under the PRISMA guidelines. RESULTS: Out of 2217 screened studies, 22 met our inclusion criteria, and 6 qualified for meta-analysis. The strategies included various designs of saddles, changes in the cycling position, seat shock absorber, shorts with different padding, using the recumbent bike. Using the no-nose saddle and recumbent bike resulted in a significant reduction of perineal pressure and higher penile oxygen pressure compared with a standard saddle. Indirect evidence supports the protective effect of standing on the pedals every few minutes during cycling. More evidence is needed to support-or dismiss-other strategies. CONCLUSIONS: Current evidence supports the use of no-nose saddles as a mean to reduce the negative impact of cycling on the perineum in healthy males at the cost of worse stability and increase of posterior seat pressure. Standing on the pedals every ten minutes might be an effective and potentially widely applicable strategy. The use of a recumbent bike appears to protect the perineum, but several concerns prevent its widespread use.

Changes in the composition of the human intestinal microbiome in alcohol use disorder: a systematic review.

Background: A growing body of evidence highlights the role of the intestine in the development of various alcohol use disorder (AUD) complications. The intestinal microbiome has been proposed as an essential factor in mediating the development of AUD complications such as alcoholic liver disease.Objectives: To provide a comprehensive description of alcohol-induced intestinal microbiome alterations.Methods: We conducted a systematic review of studies investigating the effect of alcohol on the intestinal microbiome using the PRISMA checklist. We searched the Medline database on the PubMed platform for studies determining the effect of alcohol on microbiota in individuals with AUD. The manual search included references of retrieved articles. Only human studies examining the intestinal bacterial microbiome using 16S ribosomal RNA sequencing were included. Data comparing relative abundances of bacteria comprising intestinal microbiota was extracted.Results: We retrieved 17 studies investigating intestinal microbiome alterations in individuals with AUD. Intestinal microbiome alterations in individuals with AUD included depletion of Akkermansia muciniphila and Faecalibacterium prausnitzii and an increase of Enterobacteriaceae. At the phylum level, a higher abundance of Proteobacteria and lower of Bacteroidetes were found. Mixed results regarding Bifidobacterium were obtained. Several species of short-chain fatty acids producing bacteria had a lower abundance in individuals with alcohol use disorder.Conclusion: Intestinal microbiome alterations associated with dysbiosis in individuals with AUD are generally consistent across studies, making it a promising target in potential AUD complications treatment.